Dioxin alters ability to fight infection, mouse study finds.
|
Hogaboam, J, A Moore and BP Lawrence. 2008. The aryl hydrocarbon receptor affects distinct tissue compartments during ontogeny of the immune system. Toxicological Sciences 102(1):160-170. |
![]() |
| John Morgan/Flickr |
Context
Dioxins are a family of structurally related chemicals. They are mainly produced as byproducts during manufacturing processes and the burning of garbage, medical wastes and other materials. Dioxins cause cancer, affect reproduction and development and harm the immune system. Health symptoms noted after workplace and accidental exposures include skin rashes called chloracne, tiredness and metabolic changes.
Dioxins are persistent organic pollutants; once released into the environment they degrade slowly, if at all. The chemicals can travel in the atmosphere and return to Earth with rain and snow. They may land in water, on land or on plants and travel up the food chain, where they eventually bioaccumulate in people and other top predators.
The main route of human exposure is through diet, particularly fatty ones rich in red meat and dairy products. A low-fat diet is one way to reduce exposure. A diet rich in vegetables not only lessens dioxin exposure but may also counteract its harmful effects. Compounds found in certain foods, such as broccoli, cauliflower and green tea, have been found by cell and animal studies to limit, and in some cases, antagonize dioxin's effects.
Dioxin levels are typically reported as parts per trillion (ppt), which less than a drop of water in an Olympic-sized swimming pool. Levels of the environmental pollutant have dropped considerably in recent years. Average levels in people are now less than 10 parts per trillion. Levels in more than half of the US population are below detection. Nevertheless, certain "hot-spots" have considerably higher levels. The EPA found that portions of the Saginaw River in Michigan, downstream of a Dow Chemical plant, registered dioxin levels of 1.6 million parts per trillion.
Animals breakdown and eliminate dioxin differently. Mice, for example, can process the pollutant in 7-14 days (for TCDD, the most potent dioxin) whereas humans take 14 years to eliminate the same amount. The faster turn-around in mice makes them good study models for determining dioxin's health effects.
Animal and human epidemiological studies show that dioxin causes a wide variety of health effects, including reproductive problems, skin diseases, cancer and immune suppression. Adult mice given dioxin have a reduced capacity to fight an influenza infection (Lawrence et al. 2000; Warren et al. 2000).
PCBs have chemical properties similar to dioxin, so study results of PCBs are helpful for effects comparisons. An epidemiological study by the Dutch health service correlated child health outcomes to the levels of PCBs in their mother’s breast milk. They found that a higher exposure to PCBs resulted in children being more susceptible to viral ear infections during their early years (Koopman-Esseboom et al. 1996; Weisglas-Kuperus et al. 1995, 2000).
This study looked at the long term immune effects of dioxin when exposure occurs during development. The authors tried to identify the critical windows of exposure where fetuses are most sensitive to dioxin's harmful effects.
Pregnant mice were given a dose of 1,000 ppt dioxin either: 1) throughout gestation (days 0, 7 and 14) and lactation (day 2 after birth); 2) gestation only (days 0, 7 and 14); 3) lactation only (day 2); or 4) late during gestation (day 14) and continuing on during lactation (day 2).
After exposure, the pups and their mother’s were kept dioxin free for the rest of their lives. At 8 weeks, the pups and their moms were infected with a non-lethal dose of the influenza virus. One week later, lung tissue was collected and analyzed for the number and types of white blood cells. Inflammation factors produced in the lungs by the white blood cells were measured.
What did they find?
The number of specialized white blood cells -- referred to as CD8+ T-cells specifically recognize and kill the flu virus, were significantly reduced in the pups but not their moms, who had been exposed to dioxin.
There were slight, but significant differences depending on when exposure to dioxin occurred. The most severe reduction in CD8+ T-cells was seen when dioxin was given only while the pups were nursing.
In comparison, the number of a different type of white blood cell, called a neutrophil, was significantly increased in the dioxin-exposed pups. The neutrophils, which contribute to lung tissue swelling, were most severely increased when dioxin was given late in gestation and during lactation.
Neutrophils are important mediators of inflammation. Inflammation is needed to clear infections from the body. Too much inflammation, though, can be harmful because it can lead to other health complications, such as bronchitis, sinus and ear infections and pneumonia, or it can aggravate chronic medical conditions, such as asthma, diabetes and heart disease.
The mothers of the pups mounted a normal immune response to the influenza infection with no decrease in CD8 T-cells or increase in neutrophils.
What does it mean?
Dioxin exposure in the womb, and/or during nursing, impacts the development of the immune system in mouse pups. Ultimately, the immune system of the pups is permanently changed such that their response to an infection later in life is seriously impaired.
These results demonstrate the importance of the critical windows of exposure for dioxin induced immune suppression: there are periods in life where individuals are especially sensitive to exposure to harmful chemicals potentially resulting in long-term changes and/or reprogramming that affect normal biological responses later in life.
In this study, the pup’s response to influenza infection was remarkably affected even though the pup's were only exposed a few times to a low level before birth and during nursing. Because of the short exposures (versus continuous, long-term exposures), the immune changes most likely occurred during important early developmental stages, since most of the dioxin in the pups examined would have been excreted by the time they were 8 weeks old. The dose experienced by the pups was also considerably lower than that required to affect an adult mouse's response to influenza (Lawrence et al. 2000).
While dioxin levels in the environment have dropped considerably in recent years from their peak in the late 1970’s, these results demonstrate that continued reduction measures and remediation efforts in contaminated areas are warranted. Moreover, we know enough to say that women of child-bearing age need to be especially vigilant in the foods they choose to both avoid increasing their risk of exposure and also potentially decrease the harmful effects of prior exposure. As with many health recommendations, lean cuts of beef, low fat dairy products, and lots of fruits and vegetables are suggested to minimize risk of dioxin and PCB exposure.
ResourcesWHO. Dioxins and their effects on human health. Inflammation 101: Frequently asked questions. KidsHealth. The immune system. Koopman-Esseboom et al. 1996. Effects of polychlorinated biphenyl/dioxin exposure and feeding type on infants' mental and psychomotor development. Pediatrics 97(5):700-6. Lawrence, BP, TK Warren and H Luong. 2000. Fewer T lymphocytes and decreased pulmonary influenza virus burden in mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Journal of Toxicology and Environmental Health, Part A 61(1):39-53. Warren, TK, KA Mitchell and BP Lawrence. 2000. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses the humoral and cell-mediated immune responses to influenza A virus without affecting cytolytic activity in the lung. Toxicological Sciences 56(1): 114-23. Weisglas-Kuperus et al. 1995. Immunologic effects of background prenatal and postnatal exposure to dioxins and polychlorinated biphenyls in Dutch infants. Pediatric.Research 38(3):404-410. Weisglas-Kuperus et al.2000., Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children. Environmental Health Perspectives 108(12):1203-7. |
Dioxin


